Biomedical Engineering Reference
In-Depth Information
6.2.1 Functional groups-Modified Chitosan
6.2.1.1 N-Alkylated Chitosan
Chitosan has a number of hydroxyl and amino groups along its molecular chain. These
groups provide so much hydrogen bonding (H-bonding) between adjacent chains that
chitosan cannot dissolve in neutral aqueous solution. This largely limits its clinical appli-
cations, for example, in the DDS. Alkylated chains were introduced into chitosan to
break the strong interaction of neighboring molecules and make it soluble in a pH 7.4
environment [23]. By doing this, hydrophobic interactions are strengthened, and chito-
san may become a candidate hydrophobic drug carrier for delivering drugs such as bleo-
mycin with palmitoyl chains and taxol and vitamin B
2
(VB
2
) with dodecyl chains [24]. Tien
et al. [25] prepared N-acylated chitosan to introduce hydrophobicity for use as a matrix for
drug delivery. It was found that derivatization reduced the hydration of the matrix and
played a role in network stabilization by hydrophobic interactions. Acylation with longer
side chains resulted in a higher degree of order and crushing strength but lower swelling.
Drug dissolution kinetics showed longer release times for higher degrees of functionaliza-
tion. Moreover, it was also reported that alkylated chitosan was proposed as a nonviral
vector for gene transfection, because hydrophobic chains could weaken the strong interac-
tions between primary amino groups and phosphate groups, which was reported to resist
DNA unpacking within the cell to a certain degree [26]. As a result, transfection efficiency
could be considerably increased by the incorporation of hydrophobic moieties.
Synthesis methods of N-alkylated chitosan have been reported by many groups. One
common method is to dissolve chitosan in acetic acid and mix an aliphatic aldehyde into
the solution subsequently. Through the addition of excess NaBH
4
, the Schiff base formed
is reduced and this leads to the final alkylation of chitosan [27] (
cf
. Figure 6.1). Another
commonly used method was reported by Yao and coworkers [28]. Alkylated chitosans
were prepared by modifying chitosan with alkyl bromide (
cf
.
Figure 6.2).
6.2.1.2 Thiolated Chitosan
Thiol groups were introduced into chitosan. One motive is to enhance the mucoadhesive
properties of chitosan. Thiolated chitosan has shown strong mucoadhesive properties by
forming disulfide bonds with cysteine-rich domains of mucus glycoproteins, leading to
an improvement in mucoadhesion of up to 140-fold that of unmodified chitosan [29]. The
localization of a DDS at a given target site (i.e., nasal mucosa) was guaranteed and per-
meation of drugs was enhanced in this way. The study by Krauland et al. [30] showed
that the bioavailability of an insulin-loaded chitosan-based vehicle via nasal administra-
tion was significantly greater for a thiolated chitosan carrier than for an unmodified
CH
2
OH
CH
2
OH
CH
2
OH
H
OH
OH
H
OH
H
H
35°C
NaBH
4
H
OH
H
OH
H
OH
O
+O
C
R
H
O
O
H
H
4h
n
n
n
H
NH
2
H
NH
H
N
H
R
H
RH
Figure 6.1
N
-alkylated chitosan prepared via Schiff base reduction.
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